Laparoscopy in Gynecologic Malignancies: Page 2 of 2
Laparoscopy in Gynecologic Malignancies: Page 2 of 2
The recommended FIGO staging system for cervical cancer is a clinical one. The role of surgery in primary management is reserved for the treatment of early-stage disease. Patients whose disease is confined to the cervix, with or without upper vaginal involvement, are often treated with a radical hysterectomy and bilateral pelvic lymphadenectomy. Patients who have more advanced disease generally receive radiation therapy with or without chemotherapy. Over the past few years, several authors have investigated the use of laparoscopy for both the treatment of early-stage disease and the surgical staging of advanced disease.
Treatment of Early-Stage Disease
Two different laparoscopic approaches have been used in the treatment of early-stage cervical cancer. In the first approach, laparoscopy is used to perform a bilateral pelvic lymphadenectomy, transect the upper uterine attachments, and divide the uterine vessels. The procedure is completed vaginally using a modified version of the Schauta radical vaginal hysterectomy.
The second method involves the performance of a radical hysterectomy and bilateral pelvic lymphadenectomy almost completely through the laparoscope. Although the two approaches differ in many aspects, they both must be considered experimental, since neither method has been adequately studied, and only a few surgeons in the world are fully qualified to perform either one.
Laparoscopic-Assisted Radical Vaginal Hysterectomy—In 1991, Querleu and colleagues described their transperitoneal laparoscopic approach to pelvic lymphadenectomy in early-stage cervical cancer. They performed laparoscopic pelvic lymph node dissections in 39 patients. The dissection was limited to the area below the common iliac vessels, with a mean of 8.7 lymph nodes removed per patient. Subsequently, 33 patients underwent a laparotomy with radical hysterectomy and removal of all remaining lymph node tissue. No residual lymph node metastases were found.
With the apparent thoroughness of laparoscopic lymph node dissection, investigators then began combining laparoscopic lymphadenectomy with modifications of the Schauta radical vaginal hysterectomy for the treatment of early cervical cancer as an alternative to traditional radical abdominal hysterectomy with pelvic lymphadenectomy. However, even surgeons who have extensive experience with the Schauta technique do not perform the entire radical hysterectomy vaginally.
To date, over 250 cases of laparoscopic-assisted radical vaginal hysterectomy (LARVH) have been reported. In 1993, Dargent and colleagues presented not only one of the largest series of LARVH (51 cases) but also the one with the longest follow-up. They reported a 3-year actuarial survival rate of 95.5% for patients with node-negative, stage IB or IIA disease. Furthermore, no patient developed urinary tract fistulas or needed reoperation for complications.
The more limited American experience with LARVH differs somewhat from that of Dargent et al. This difference reflects the fact that the majority of gynecologic oncologists in the United States have never performed a radical vaginal hysterectomy. In the largest American series, Hatch et al reported a mean operative time of 225 minutes (Table 1). In their 37 cases, there were 2 bladder injuries, 2 ureterovaginal fistulas, and 1 large-bowel injury, for a major complication rate of 14%.
Thus, although LARVH seems to be feasible, and its successful completion appears to reduce blood loss, decrease febrile morbidity, and shorten hospital stays when compared to traditional abdominal radical hysterectomy, the relatively high major complication rate highlights many of the substantial questions that remain regarding the safety of the procedure (Table 1).
Laparoscopic Lymphadenectomy Plus Radical Vaginal Trachelectomy—Perhaps the most ingenious application of laparoscopy in the management of early cervical cancer was initiated by Dargent et al in 1987. In women who desired to maintain their fertility, they combined laparoscopic pelvic lymphadenectomy with radical vaginal trachelectomy (Table 1). By retaining the body of the uterus, these women preserved their reproductive function while theoretically receiving a satisfactory oncologic procedure.
Currently, a total of 62 such procedures have been reported in the world literature, and over a dozen healthy babies have been born from women who have undergone the procedure. Thus far, there have been only four documented recurrences.
The GOG recently closed a prospective trial evaluating laparoscopic lymphadenectomy in patients with early-stage cervical cancer. The 73 enrolled patients underwent immediate laparotomy after laparoscopic pelvic and para-aortic lymph node sampling. The results and conclusions of the trial are not yet available. Although this GOG study will not be able to address any issues related to the safety and efficacy of radical vaginal hysterectomy or radical vaginal trachelectomy, it may be the first step in answering some of the questions about the thoroughness and adverse effects of laparoscopic lymphadenectomy in these patients.
Laparoscopic Radical Hysterectomy was first described by Canis et al and Nezhat et al in 1992. These initial reports were criticized due to the length of the procedure (8 and 7 hours, respectively) and lymph node yield (10 and 14 pelvic nodes removed, respectively). More recent reports have demonstrated shorter operative times and higher lymph node yields.
Spirtos and colleagues recently presented the largest series of laparoscopic radical hysterectomy to date (Table 1). In this series, 43 patients underwent laparoscopic radical hysterectomy with aortic and pelvic lymphadenectomy. The average operating time was 225 minutes, with an average blood loss of 250 mL. The mean number of lymph nodes removed was 32 (range, 19 to 65). One patient suffered an intraoperative cystotomy, which was repaired laparoscopically, and another developed a postoperative ureterovaginal fistula, which required a reoperation. There has been one documented recurrence.
Although the English literature currently contains fewer than 100 reported cases of laparoscopic radical hysterectomy, the technique offers many potential advantages over LARVH. First, US gynecologic oncologists have much greater experience performing a traditional radical abdominal hysterectomy than a radical vaginal hysterectomy. Therefore, performance of a laparoscopic radical hysterectomy would require mastering the use of new surgical tools, rather than learning an entirely new, very difficult procedure.
Second, even for the most experienced vaginal surgeon, visualization of essential structures can be difficult during a radical vaginal hysterectomy. This problem should very rarely occur during a laparoscopic radical hysterectomy.
Finally, LARVH frequently requires perineal or vulvar incisions to facilitate the dissection. These quite painful incisions are avoided with the laparoscopic radical hysterectomy technique.
Table 1 compares the results of the largest recent series that employed the various approaches to radical hysterectomy.
Staging of Advanced-Stage Disease
As stated previously, the FIGO staging system for cervical cancer is a clinical one, and the standard management for patients who present with advanced disease does not include surgery for staging or treatment. However, over 30% of patients with advanced disease are inaccurately staged by clinical methods. For this reason, many investigators have studied the role of pretreatment surgical staging in these patients.
The pretreatment surgical staging of cervical cancer is based on its known pattern of lymphatic spread and, therefore, involves bilateral retroperitoneal lymph node assessment. The main proposed benefit of pretreatment staging is that it provides a more accurate definition of the extent of disease spread so that irradiation and/or chemotherapy can be better individualized.
The disadvantages relate to the morbidity associated with a major surgical procedure that gives information that will benefit fewer than 10% of patients undergoing the operation. Furthermore, a prolonged recovery period after pretreatment laparotomy can lead to significant delays in the initiation of definitive therapy.
Due to these disadvantages, the pretreatment surgical staging of patients with advanced cervical cancer remains a controversial issue. Adding to the controversy, many authors are now reporting the use of operative laparoscopy for pretreatment surgical staging. The purported advantage of the laparoscopic approach is that it provides the same delineation of the extent of disease as is achieved with laparotomy, but with less morbidity and essentially no delay in the initiation of definitive therapy.
One of the most significant problems with pretreatment laparotomy is the subsequent formation of intraabdominal adhesions that can lead to significant postirradiation enteric morbidity. This morbidity can be reduced if the laparotomy and lymphadenectomy are performed via an extraperitoneal, rather than a transperitoneal, approach. Although clinical studies have not compared adhesion formation after extraperitoneal laparotomy vs laparoscopic lymphadenectomy, animal studies have shown that the two techniques have the same incidence of adhesion formation.[37,38]
In 1992, Childers and colleagues reported the results of pretreatment laparoscopic staging in six patients with advanced cervical cancer. All of these patients had negative lymph nodes on preoperative computed tomography (CT) and underwent pelvic and para-aortic lymph node sampling. Two patients were found to have positive pelvic nodes, one of whom also had positive para-aortic nodes.
These 6 patients were part of a larger group of 18 patients with cervical cancer who underwent laparoscopic lymphadenectomy. The average number of lymph nodes removed laparoscopically in the whole group was 31, and there were no significant short-term complications.
Although this study by Childers et al demonstrated that laparoscopic pelvic lymphadenectomy was feasible and could be performed safely in patients with advanced cervical cancer, its clinical utility is debatable. Since most patients with advanced disease receive whole-pelvic radiotherapy, the status of their pelvic lymph nodes does not have any impact on their management. Therefore, most authors, including Childers and colleagues, currently sample only the high pelvic and low para-aortic lymph nodes that lie outside of the standard pelvic radiation field.[40,41] If these lymph nodes are found to be positive, the radiation field can be extended to include the para-aortic nodes and/or chemotherapy can be given.
The largest series of laparoscopic staging of advanced cervical cancer was recently reported by Chu and coworkers. Laparoscopic bilateral para-aortic lymph node dissections were performed in 28 patients. An average of eight nodes were removed per patient, and the average operation time was 95 minutes. The one complication (3.6%) was bleeding from the inferior vena cava, which required laparotomy for repair.
Ten patients (36%) had positive para-aortic nodes and were subsequently treated with extended-field radiation or chemotherapy and whole-pelvic irradiation. The patients with negative para-aortic nodes were given pelvic radiation alone. With a short mean follow-up of 18 months, only one patient has suffered a recurrence.
This series by Chu et al again demonstrates the feasibility of laparoscopic lymphadenectomy but also underscores the dearth of studies with large patient numbers and long-term follow-up. The GOG trial that is evaluating laparoscopic lymphadenectomy in women with early cervical cancer was originally proposed to also include laparoscopic staging for patients with advanced disease. However, the protocol was later amended to investigate only those patients with early-stage disease. Therefore, it is unlikely that the questions regarding the safety of preirrad-iation laparoscopic staging will be answered anytime in the foreseeable future.
The majority of women with endometrial cancer present with disease that is clinically confined to the uterus. Surgical removal of the uterus is the most important step in the treatment of these patients. However, over 20% of patients with endometrial cancer apparently confined to the uterus will be found to have disease outside the uterus at staging laparotomy. Therefore, the staging system recommended by FIGO is a surgical one that requires peritoneal washings, removal of the uterus and adnexae, and retroperitoneal lymph node sampling.
For patients with endometrial cancer, the status of the pelvic and para-aortic lymph nodes is the most significant piece of staging information that bears on future prognosis and further therapy. Although most of the original series of laparoscopic lymph node dissection described the use of the procedure in patients with cervical cancer, its greatest clinical utility may be in women with endometrial cancer.
Laparoscopic-Assisted Surgical Staging
By combining operative laparoscopy with simple vaginal hysterectomy, laparoscopic-assisted surgical staging (LASS) has been proposed as an alternative to laparotomy for patients with early endometrial cancer. With a LASS procedure, operative laparoscopy allows for the assessment of the peritoneal cavity, the ability to obtain peritoneal washings, and the guaranteed removal of the adnexae.
Most importantly, lymph node sampling can also be performed laparoscopically in indicated cases. (Indications vary depending on the institution but generally include those cases with high-grade tumors and/or tumor invasion to the outer half of the myometrium). The uterus, cervix, and attached adnexae are removed during the vaginal portion of the procedure as in a laparoscopic-assisted vaginal hysterectomy (LAVH) for benign disease.
Childers and colleagues published the first series of LASS procedures for endometrial cancer in 1993. A total of 59 patients with endometrial carcinoma clinically confined to the uterus underwent laparoscopic evaluation. Six patients were found to have intraperitoneal disease and did not undergo further laparoscopic staging.
Of the remaining 53 patients, 52 underwent an LAVH and 29 were considered candidates for laparoscopic lymph node sampling. The lymphadenectomy was performed successfully by laparoscopy in 93% of these patients. The estimated blood loss was less than 200 mL per patient, and the average hospital stay was 2.9 days.
Although this study demonstrated the feasibility of the LASS procedure and identified obesity as a limiting factor, the number of lymph nodes removed laparoscopically, the comparative costs of the procedure, and long-term follow-up were not discussed.
Many of these issues have been addressed recently. Gemignani and coworkers compared the clinical outcomes and hospital charges for 320 patients with endometrial cancer who were staged by laparoscopy vs traditional laparotomy. The patients managed laparoscopically had significantly fewer complications, shorter hospitalizations, and lower overall hospital charges than those who underwent laparotomy. Furthermore, there was no statistically significant difference in recurrence rates between the two groups.
An earlier series of 44 patients presented by Boike et al demonstrated similar findings, and reported no statistical difference in the total number of lymph nodes removed by laparoscopy compared to laparotomy.
The safety, efficacy, and cost savings of LASS are currently being evaluated in a prospective manner. The GOG is performing a randomized, phase III trial designed to compare the differences between LASS vs staging laparotomy in the management of women with early endometrial cancer. Variables that will be assessed include adequacy of staging, complications, operative time, hospital stay, total procedural costs, and quality of life.
Staging of Patients Who Were Incompletely Staged Initially
A second application of operative laparoscopy is the staging of endometrial cancer patients who were incompletely staged initially. Gynecologic oncologists are frequently faced with the problem of recommending further management for a patient with endometrial cancer who had a hysterectomy but did not receive adequate surgical staging. Given this dilemma, the clinician has traditionally had one of three options: (1) recommend no adjuvant therapy, thereby risking potential undertreatment; (2) offer adjuvant therapy, risking possible overtreatment; or (3) perform a thorough staging laparotomy, subjecting the patient to its associated potential morbidity, mortality, and delayed adjuvant treatment.
Childers et al recently described a fourth option. They reported on a series of 13 patients with incompletely staged endometrial cancer who underwent laparoscopic staging. Extrauterine disease was found in three patients (23%), and an average of 17.5 lymph nodes were removed per patient. There were no introperative complications, the average estimated blood loss was less than 50 mL, and the mean hospital stay was 1.5 days. Although this small series does not confirm the value of laparoscopic staging, it does demonstrate that, in highly skilled hands, it can be completed safely and successfully.
The GOG is currently evaluating the feasibility and adverse effects of laparoscopic staging in patients with incompletely staged endometrial cancer. Pending the results of this trial, laparoscopic staging of patients with incompletely staged endometrial cancer should be performed only in an investigational setting.
Numerous technologic and surgical advances have led to the application of operative laparoscopic techniques in the management of patients with gynecologic cancers. Operative laparoscopy has been described in the surgical staging and treatment of patients with ovarian, cervical, and endometrial cancers. It appears to be a very promising approach with the potential to revolutionize numerous aspects of the management of gynecologic malignancies.
However, despite all of the enthusiasm for the use of laparoscopy for gynecologic malignancies, its potential is unconfirmed and its hazards are unknown. Reports regarding complications and long-term results are just now beginning to surface.[48,49] More clinical data are required before the minimally invasive techniques can be accepted as new surgical standards.
Ongoing, prospective clinical trials will help answer many of the questions regarding safety and efficacy of laparoscopic procedures. Until more data accumulate, operative laparoscopy will remain a promising, but unproven, tool in the management of patients with gynecologic malignancies.
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